Ample evidence has been accumulated that cytokines, a class of soluble mediators involved in cell-to-cell "communications," are essential in the regulation of the immune system. It has been known that cytokines induce proliferation, differentiation and activation of target cells through interaction with specific cell surface receptor(s). Interleukin-2 (IL-2), previously defined as T cell growth factor (Morgan, D. A., et al., Science 198:1007 (1976)), is one of the best characterized cytokines and is known to play a pivotal role in the antigen-specific clonal proliferation of T lymphocytes (T cells) (Smith, K. A., Ann. Rev. Immunol. 2:319 (1984); Taniguchi, T., et al., Immunol. Rev. 92:121 (1986)). IL-2 also appears to act on other cells of the immune system such as immature thymocytes (Raulet, D. H., Nature 314:101 (1985)), B lymphocytes (B cells) (Tsudo, M., et al., J. Exp. Med. 160:612 (1984); Waldmann, T. A., et al., J. Exp. Med. 160:1450 (1984); Blackman, M. A., et al., Cell 47:609 (1986)), macrophages (Malkovsky, M., et al., Nature 325:262 (1987)), natural killer cells (NK cells) (Henney, C. S., et al., Nature 291:335 (1981)), and lymphokine-activated killer cells (LAK cells) (Lotze, M. E., et al., Cancer Res. 41:4420 (1981); Grimm, E. A., et al., J. Exp. Med. 155:1823 (1982)). These multifunctional properties of IL-2 have now opened up possibilities in the formulation of immunotherapies such as adoptive immunotherapy (Rosenberg, S. A., et al., N. Engl. J. Med. 316:889 (1987)). More recently, IL-2 has been shown to function also on neural cells such as oligodendrocytes (Benveniste, E. N., et al., Nature 321:610 (1986)), suggesting a possible involvement of this cytokine in the central nervous system. Despite extensive studies on the IL-2 system in the context of basic and clinical immunology, information has been limited on the molecular mechanism(s) underlying the IL-2-mediated signal transduction (LeGrue, S. J., Lymphokine Res. 7:1987 (1988); Millis, G. B., et al., Cell 55:91 (1988); Valge, V. E., et al., Cell 55:101 (1988); Tigges, M. A., et al., Science 243:781 (1989)).
The IL-2 receptor (IL 2R) is known to be uniquely present in three forms: high-, intermediate- and low-affinity forms with respect to its binding ability to IL-2, and respective dissociation constants (Kds) of 10.sup.-11 M, 10.sup.-9 M, and 10.sup.-8 M (Robb, R. J., et al., J. Exp. Med. 160:1126 (1984); Tsudo, M., et al., Proc. Natl. Acad. Sci. USA 83:9694 (1986); Teshigawara, K., et al., J. Exp. Med. 165:223 (1987)). Following the characterization of IL-2R.alpha. chain (Tac antigen, p55) (Leonard, W. J., et al., Nature 311:626 (1984); Nikaido, T., et al., Nature 311:631 (1984); Cosman, D., et al., Nature 312:768 (1984)), it became evident that the .alpha. chain constitutes solely the low-affinity form and it is not functional per se in IL-2 internalization and signal transduction, unless associated with another specific membrane component(s) of lymphoid cells (Hatakeyama, M., et al., Nature 318:467 (1985); Greene, W. C., et al., J. Exp. Med. 162:363 (1985); Kondo, S., et al., J. Exp. Med. 320:75 (1986); Robb, R. J., Proc. Natl. Acad. Sci. USA 83:3992 (1986)). Subsequently, the lymphoid membrane component was identified to be a novel receptor chain, termed .beta.-chain (or p70-75) (Tsudo, M., et al., Proc. Natl. Acad. Sci. USA 83:9694 (1986); Teshigawara, K., et al., J. Exp. Med. 165:223 (1987); Sharon, M., et al., Science 234:859 (1986); Robb, R. J., et al., Proc. Natl. Acad. Sci. USA 84:2002 (1987); Tsudo, M., et al., Proc. Natl. Acad. Sci. USA 84:4215 (1987); Dukovich, M., et al., Nature 327:518 (1987)). In fact, experimental evidence has suggested that the IL-2R.beta. chain per se constitutes the intermediate-affinity form (Tsudo, M., et al., Proc. Natl. Acad. Sci. USA 83:9694 (1986); Teshigawara, K., et al., J. Exp. Med. 165:223 (1987)). In addition, its association with the IL-2R.alpha. chain results in the high-affinity form of the receptor (Tsudo, M., et al., Proc. Natl. Acad. Sci. USA 83:9694 (1986); Teshigawara, K., et al., J. Exp. Med. 165:223 (1987); Sharon, M., et al., Science 234:859 (1986); Robb, R. J., et al., Proc. Natl. Acad. Sci. USA 84:2002 (1987); Tsudo, M., et al., Proc. Natl. Acad. Sci. USA 84:4215 (1987); Dukovich, M., et al., Nature 327:518 (1987)). Expression studies using wild-type and mutated IL-2R.alpha. chain cDNAs strongly support the notion that the IL-2R.beta. chain but not the IL-2R.alpha. chain possesses a domain(s) responsible for driving the intracellular signal transduction pathway(s) (Hatakeyama, M., et al., J. Exp. Med. 166:362 (1987); Kondo, S., et al., Nature 327:64 (1987)). There exists, therefore, a need to obtain IL-2.beta. chain in amounts which will enable its structure and function to be elucidated, this being an essential step in gaining further insight into the molecular basis of the high-affinity of IL-2R as well as on the mechanism of signal transduction operating in IL-2 responsive cells.